In this account of early practitioners and advocates of 'inoculation,' or the use of tiny amounts of smallpox contagion to induce a mild case of smallpox and immunity, author Carrell weaves prodigious historical research with fictionalized dialogue to create a tale of two prominent figures: Lady Mary Wortley Montagu of London and Dr. Zabdiel Boylston of Boston. Both Lady Mary and Boylston suffered scarring from smallpox, and, by living in the early 18th century, both witnessed the devastation of epidemics in terms of public health and private loss.

Both were also aware of the use of inoculation to prevent severe disease in Turkey (Lady Mary visited with her ambassador husband) and in Africa (on the advice of Cotton Mather, Boylston interviewed Africans, slave and freemen, living in Boston). Both faced formidable challenges and risked personal security to promote the use of this technique. Both proved their belief in the technique by the inoculation of their own children. And both, perhaps, met. At the behest of the Royal Society, Boylston traveled to London, witnessed numerous inoculations, and presented his Boston experience to the Society.

The book also chronicles the natural course of the disease, its various symptoms, forms and popular treatments, and the political impact of smallpox on the royal families of Europe and business interests in Boston. The medical research of various doctors is detailed. In particular, selected Newgate prisoners were offered pardon in return for participation in an experiment conducted by Mr. Maitland, who also inoculated Lady Mary's children. These experiments were used to test the safety and efficacy of inoculation prior to royal inoculation.

Ultimately, detractors of inoculation ceased their vitriolic attacks, as the risks of inoculation were proven to be far lower than exposure without such protection. The success of inoculation paved the way for Edward Jenner, often called 'the father of immunology,' to successfully use cowpox to induce smallpox immunity later in the 18th century.